Method and apparatus for preventing cardiac arrhythmias with endovascular stimulation

ABSTRACT

Certain cardiac arrhythmias can be prevented by appropriate electrical stimulation of autonomic nerves innervating the heart. An implantable cardiac rhythm management device is configured to deliver such stimulation when an autonomic imbalance is predicted to be present via an endovascular electrode. Autonomic imbalance may be predicted to be present based upon circadian rhythms, detected heart rates, or detected heart rate variability.

CROSS REFERENCE TO RELATED APPLICATION(S)

This application is a continuation of U.S. patent application Ser. No.10/105,941, filed on Mar. 25, 2002, now U.S. Pat. No. 7,123,959, thespecification of which is incorporated herein by reference.

FIELD OF THE INVENTION

This invention pertains to methods and apparatus for the management ofcardiac rhythm disorders.

BACKGROUND

Tachyarrhythmias are abnormal heart rhythms characterized by a rapidheart rate, typically expressed in units of beats per minute (bpm). Theycan occur in either chamber of the heart (i.e., ventricles or atria) orboth. Examples of tachyarrhythmias include sinus tachycardia,ventricular tachycardia, ventricular fibrillation (VF), atrialtachycardia, and atrial fibrillation (AF). Tachyarrhythmias can be dueto abnormal excitation by normal pacemaker tissue, an ectopic excitatoryfocus, or a re-entry phenomenon. Tachycardia occurs when the heartcontracts relatively normally but at a rapid rate, while fibrillationoccurs when the chamber depolarizes in a chaotic fashion with abnormaldepolarization waveforms as reflected by an EKG.

An electrical defibrillation shock applied to a heart chamber can beused to terminate most tachyarrhythmias by depolarizing excitablemyocardium and rendering it refractory. Implantablecardioverter/defibrillators (ICDs) provide this kind of therapy bydelivering a shock pulse to the heart when fibrillation is detected bythe device. ICDs can be designed to treat either atrial or ventriculartachyarrhythmias, or both, and may also incorporate cardiac pacingfunctionality. The most dangerous tachyarrhythmias are ventriculartachycardia and ventricular fibrillation, and ICDs have most commonlybeen applied in the treatment of those conditions. Another type ofelectrical therapy for tachycardia is antitachycardia pacing (ATP). InATP, the heart is competitively paced with one or more pacing pulses inan effort to interrupt the reentrant circuit causing the tachycardia.Modern ICD's usually have ATP capability so that ATP therapy isdelivered to the heart when a tachycardia is detected, while a shockpulse is delivered when fibrillation occurs.

ICDs are also capable of detecting atrial tachyarrhythmias, such asatrial fibrillation and atrial flutter, and delivering a shock pulse tothe atria in order to terminate the arrhythmia. Although not immediatelylife-threatening, it is important to treat atrial fibrillation forseveral reasons. First, atrial fibrillation is associated with a loss ofatrio-ventricular synchrony which can be hemodynamically compromisingand cause such symptoms as dyspnea, fatigue, vertigo, and angina. Atrialfibrillation can also predispose to strokes resulting from emboliforming in the left atrium. Although drug therapy and/or in-hospitalcardioversion are acceptable treatment modalities for atrialfibrillation, ICDs configured to treat atrial fibrillation offer anumber of advantages to certain patients, including convenience andgreater efficacy.

As described above, an implantable device may deliver appropriatetherapy to terminate certain detected arrhythmias. Such therapies arenot invariably successful, however, and, even when they are, may requirerepeated application until the arrhythmia is finally terminated.Defibrillation shocks also subject the patient to some discomfort. Itwould be more beneficial if an implantable device could detect when apre-arrhythmic condition exists and deliver electro-stimulatory therapyin a manner that prevents the arrhythmia from occurring in the firstinstance.

SUMMARY OF THE INVENTION

The present invention relates to an implantable cardiac rhythmmanagement device having an autonomic stimulation channel forelectrically stimulating sympathetic or parasympathetic nerves in orderto prevent the onset of arrhythmias in susceptible patients. In thosepatients, increased relative activity of either sympathetic orparasympathetic nerves acting on the heart can be responsible fortriggering the onset of arrhythmic episodes. In accordance with theinvention, stimulation of either sympathetic or parasympathetic nervesinnervating the heart can be used to restore autonomic balance andprevent such triggered episodes. The autonomic stimulation channelincludes a pulse generator and an endovascular electrode for stimulatingnerves that lie adjacent a blood vessel within which the electrode isdisposed. The device may be configured to deliver such autonomicstimulation when an autonomic imbalance is detected by monitoring heartrate or heart rate variability. Autonomic stimulation may also bedelivered at timed intervals when autonomic imbalance is predicted to bepresent according to circadian rhythms.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of an exemplary cardiac rhythm managementdevice for delivering autonomic stimulation.

FIG. 2 illustrates an exemplary scheme for delivering autonomicstimulation.

DETAILED DESCRIPTION

Autonomic imbalance may be a factor in the development of cardiacarrhythmias in some patients. Such an imbalance refers to the relativeactivity of the sympathetic and para-sympathetic arms of the autonomicnervous system. Sympathetic and parasympathetic nerves act on the heartvia beta-adrenergic and muscarinic receptors, respectively, to affectboth heart rate and the velocity at which excitation is conductedthrough the heart. Both of these effects may contribute to thedevelopment of arrhythmias under certain circumstances in individualsotherwise so disposed.

It is well-known, for example, that an increase in the activity of thesympathetic nervous system can make the onset of such arrhythmias morelikely and may serve as a trigger for such events in certain patients.In one of its aspects, the present invention provides an implantablecardiac rhythm management device that counteracts the arrhythmogeniceffects of increased sympathetic activity by electrically stimulatingthe parasympathetic nerves innervating the heart with an endovascularelectrode. Such a device may utilize a bipolar electrode incorporatedinto a lead adapted for transvenous insertion, such as into the superioror inferior vena cava. In another embodiment, the bipolar electrode maybe incorporated within a shock lead normally used for deliveringcardioversion/defibrillation shocks to the heart. A pulse generator inthe device then delivers electrical stimulation via the bipolarelectrode to the inner surface of the blood vessel and stimulates theparasympathetic nerves that run adjacent thereto. The electricalstimulation may be, for example, in the form of a square-wave ortruncated exponential pulse train at a frequency of between 5 and 50 Hz.The result of such electrical stimulation is a slowing of sinus rhythmdue to increased parasympathetic activity acting on the sino-atrial nodeas well as a negative dromotropic effect (i.e., slowing of excitationconduction) on the atrio-ventricular node and the myocardium, both ofwhich may inhibit the triggering of an arrhythmia. In an exemplarydevice, a controller is programmed to cause delivery of parasympatheticstimulation when increased sympathetic activity is either detected orpredicted to be present. The level of sympathetic activity may beassessed by monitoring the heart rate via a ventricular sensing channelso that increased sympathetic activity is detected when the timeinterval between successive ventricular senses (i.e., RR intervals)falls below a specified minimum threshold value. In another embodiment,the level of sympathetic activity is assessed by measuring thevariability of the heart rate which is known to be influenced by therelative levels of sympathetic and parasympathetic activity. In stillanother embodiment, the controller includes a timer for delivering theparasympathetic stimulation at periodic intervals according to circadianrhythms that predict when increased sympathetic activity will bepresent. Increased parasympathetic activity can also be responsible fortriggering arrhythmias in certain individuals. These patients may betreated with an implantable device configured to stimulate sympatheticnerves when increased parasympathetic activity is detected or predictedto be present. Whether sympathetic or parasympathetic nerves arestimulated by an endovascular electrode depends upon its location. Forexample, sympathetic nerves are predominately found adjacent theanterior surface of the vena cava, while parasympathetic nerves aremostly found adjacent the posterior surface. Increased parasympatheticactivity can be detected by measurement of heart rate or heart ratevariability or can be predicted to be present according to circadianrhythms.

1. Exemplary Hardware Platform

Cardiac rhythm management devices are implantable devices that provideelectrical stimulation to selected chambers of the heart in order totreat disorders of cardiac rhythm and include pacemakers and implantablecardioverter/defibrillators. A pacemaker is a cardiac rhythm managementdevice that paces the heart with timed pacing pulses. In the descriptionthat follows, a microprocessor-based cardiac rhythm management devicewill be referred to as incorporating the system and method that is thepresent invention. In the embodiment to be described, the invention isimplemented with a controller made up of a microprocessor executingprogrammed instructions in memory. It should be appreciated, however,that certain functions of a cardiac rhythm management device could becontrolled by custom logic circuitry either in addition to or instead ofa programmed microprocessor. The terms “controller” or “circuitry” asused herein should therefore be taken to encompass either customcircuitry (i.e., dedicated hardware) or a microprocessor executingprogrammed instructions contained in a processor-readable storage mediumalong with associated circuit elements.

Implantable cardiac rhythm management devices, such as pacemakers andICD's, are electronic devices that are implanted subcutaneously on apatient's chest with leads threaded intravenously into the heart toconnect the device to electrodes used for sensing electrical activityand for electrical stimulation of the heart. FIG. 1 is a system diagramof a microprocessor-based cardiac rhythm management device with thecapability of delivering autonomic stimulation in response to detectedor predicted autonomic imbalance as well as deliveringcardioversion/defibrillation shocks and antitachycardia pacing (ATP)therapy. The device may also be configured to deliver conventionalbradycardia pacing as well. The controller 10 is a microprocessor thatcommunicates with a memory 12 via a bidirectional data bus. The memory12 typically comprises a ROM (read-only memory) for program storage anda RAM (random-access memory) for data storage. The device has atrial andventricular sensing/pacing channels that respectively include electrodes24 and 34, leads 23 and 33, sensing amplifiers 21 and 31, pulsegenerators 22 and 32, and channel interfaces 20 and 30. Incorporatedinto each sensing/pacing channel is thus a pacing channel made up of thepulse generator connected to the electrode and a sensing channel made upof the sense amplifier connected to the electrode. In this embodiment, asingle electrode is used for sensing and pacing in each channel, knownas a unipolar lead. Other embodiments may employ bipolar leads thatinclude two electrodes for outputting a pacing pulse and/or sensingintrinsic activity. The channel interfaces communicate bidirectionallywith microprocessor 10 and include analog-to-digital converters fordigitizing sensing signal inputs from the sense amplifiers and registersthat can be written to by the microprocessor in order to adjust the gainand threshold values for the sensing amplifiers, output pacing pulses,and change the pacing pulse amplitude and/or duration. An autonomicstimulation channel is provided for stimulating sympathetic orparasympathetic nerves and includes a channel interface 60, a pulsegenerator 61, and a bipolar lead with electrodes 61A and 61B. Alsoprovided are a shock pulse generator 50 with shock electrodes 51A and51B and a telemetry interface 40 for communicating with an externalprogrammer 500.

The controller 10 controls the overall operation of the device inaccordance with programmed instructions stored in memory, includingcontrolling the delivery of paces or autonomic stimulation, interpretingsense signals received from the sensing channels, and implementingtimers that may be used for various purposes. The sensing circuitry ofthe pacemaker detects a chamber sense when an electrogram signal (i.e.,a voltage sensed by an electrode representing cardiac electricalactivity) generated by a particular channel exceeds a specifieddetection threshold. A chamber sense may be either an atrial sense or aventricular sense depending on whether it occurs in the atrial orventricular sensing channel. Pacing algorithms used in particular pacingmodes employ such senses to trigger or inhibit pacing. By measuring theinterval between successive atrial and ventricular senses, thecontroller is also able to measure atrial and ventricular rates anddetect arrhythmias in those chambers using rate-based criteria.

2. Exemplary Delivery Scheme

FIG. 2 illustrates the steps involved in an exemplary scheme fordelivering autonomic stimulation for arrhythmia prevention as could beimplemented with code executed by the controller 10. Step S1 representsthe detection of atrial and ventricular senses performed by the devicein the course of its normal operation which may include bradycardiapacing as well as measurement of heart rates. Steps S2 and S3 representcomputation of intrinsic rates in the atria and ventricles bymeasurement of the time intervals between successive senses in thosechambers. Such rates may be time-averaged by appropriate filtering ofthe measured intervals. If a tachyarrhythmia is detected at step S4 inaccordance with rate-based criteria, appropriate anti-arrhythmia therapy(e.g., anti-tachycardia pacing or a defibrillation shock) may bedelivered by the device if it is configured to do so at step S5. Whetheror not such therapy is delivered, the device takes no action withrespect to autonomic stimulation if a tachyarrhythmia in the atria orventricles is detected and continues monitoring heart rates asrepresented by steps S1 and S2. If no tachyarrhythmia is detected, thecomputed atrial or ventricular rate is compared with an autonomicimbalance threshold in order to ascertain whether there is relativelyincreased activity of the sympathetic or parasympathetic nervous system.The autonomic imbalance threshold would be an upper limit for thecomputed rate in order to detect increased sympathetic activity and alower limit for detecting increased parasympathetic activity. The upperand/or lower limits making up the autonomic imbalance threshold may alsobe modified in accordance with a measured exertion level in order totake into account the effects on autonomic activity brought about bychanging metabolic demand before an autonomic imbalance warrantingintervention is declared. If such an autonomic imbalance is detected atstep S7, autonomic stimulation is delivered at step S8 through theautonomic stimulation channel. Stimulation pulses at a specifiedfrequency and for a specified time duration are output to the electrodes61 a and 61 b to thereby stimulate either sympathetic or parasympatheticnerves innervating the heart and restore cardiac autonomic balance. Asnoted earlier, autonomic stimulation may also be delivered in anotherembodiment at timed intervals when autonomic imbalance is predicted tobe present based upon known circadian rhythms.

In another embodiment, autonomic stimulation may be delivered when animbalance between sympathetic and parasympathetic activity is detectedbased upon heart rate variability. It has been found that spectralanalysis of heart rate variability can be used to determine the relativelevels of sympathetic and parasympathetic activity in a subject. Heartrate variability refers to the changes in heart rate that occur during asinus rhythm (i.e., with normally activated and conducted heartbeats)and is primarily due to the interaction of the sympathetic andparasympathetic nervous systems. Low frequency variation in heart rateis due to both parasympathetic (or vagal) and sympathetic activity,while high frequency variation is primarily due to only parasympatheticactivity. The ratio of low frequency variation to high frequencyvariation can thus be used as an indicator of the level of autonomicbalance.

As described above, a cardiac rhythm management device can be programmedto measure and collect the time intervals between successive ventricularsenses, referred to as RR intervals, for a period of time or a specifiednumber of beats. The resulting series of RR interval values can then bestored as a discrete signal and either used directly as indexed byheartbeat or resampled at a specified sampling frequency in order toequalize the time intervals. The RR interval signal can then be analyzedto determine its energies in defined high and low frequency bands. Ithas been found that the amount of signal power in a low frequency (LF)band ranging from 0.04 to 0.15 Hz is influenced by the levels ofactivity of both the sympathetic and parasympathetic nervous systems,while the amount of signal power in a high frequency band (HF) rangingfrom 0.15 to 0.40 Hz is primarily a function of parasympatheticactivity. The ratio of the signal powers, designated as the LF/HF ratio,is thus a good indicator of the state of autonomic balance, with a highLF/HF ratio indicating increased sympathetic activity, for example.Although spectral analysis of an RR interval signal can be performeddirectly in the frequency domain, a time-domain technique fordetermining the signal power in defined high and low frequency bands ispreferably used for reasons of computational economy.

Although the invention has been described in conjunction with theforegoing specific embodiment, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Such alternatives, variations, and modifications are intended to fallwithin the scope of the following appended claims.

What is claimed is:
 1. An implantable device, comprising: a pulsegenerator configurable into a parasympathetic channel for deliveringstimulation to parasympathetic nerves; a sensing amplifier configurableinto a cardiac sensing channel for measuring the patient's heart rate; acontroller programmed to detect an autonomic imbalance due to increasedsympathetic activity when a calculated ratio of low frequency to highfrequency variation in the measured heart rate is above a specifiedthreshold; and, wherein the controller is programmed to deliverparasympathetic stimulation when an autonomic imbalance due to increasedsympathetic activity is detected.
 2. The device of claim 1 wherein thecontroller is further programmed to detect a tachyarrhythmia from themeasured heart rate in accordance with rate-based criteria.
 3. Thedevice of claim 2 further comprising a shock pulse generator and whereinthe controller is further programmed to deliver shock therapy upondetection of a tachyarrhythmia.
 4. The device of claim 2 furthercomprising a pulse generator for delivering anti-tachycardia pacing andwherein the controller is further programmed to deliver anti-tachycardiapacing upon detection of a tachyarrhythmia.
 5. The device of claim 2wherein the controller is further programmed to suspend detection of anautonomic balance and delivery of parasympathetic stimulation when atachyarrhythmia is detected.
 6. The device of claim 1 wherein thecontroller is further programmed to measure atrial and ventricular ratesfrom atrial and ventricular sensing channels.
 7. The device of claim 1wherein the controller is further programmed to detect an autonomicimbalance due to increased sympathetic activity when the measured heartrate is above a higher limit value.
 8. The device of claim 7 wherein thecontroller is further programmed to modify the higher limit value inaccordance with a measured exertion level in order to take into accountthe effects of metabolic demand on autonomic activity.
 9. The device ofclaim 1 further comprising an endovascular electrode tier incorporationinto the parasympathetic stimulation channel.
 10. The device of claim 1wherein controller further comprises a timer and is configured todeliver parasympathetic stimulation at timed intervals when autonomicimbalance is predicted to be present based upon known circadian rhythms.11. A method for operating an implantable device, comprising: measuringa patient's heart rate; detecting an autonomic imbalance due toincreased sympathetic activity when a calculated ratio of low frequencyto high frequency variation in the measured heart rate is above aspecified threshold; and, delivering parasympathetic stimulation when anautonomic imbalance due to increased sympathetic activity is detected.12. The method of claim 11 further comprising detecting atachyarrhythmia from the measured heart rate in accordance withrate-based criteria.
 13. The method of claim 12 further comprisingdelivering shock therapy upon detection of a tachyarrhythmia.
 14. Themethod of claim 12 further comprising delivering anti-tachycardia pacingupon detection of a tachyarrhythmia.
 15. The method of claim 12 furthercomprising suspending detection of an autonomic balance and delivery ofparasympathetic stimulation when a tachyarrhythmia is detected.
 16. Themethod of claim 11 further comprising measuring atrial and ventricularrates from atrial and ventricular sensing channels.
 17. The method ofclaim 11 further comprising detecting an autonomic imbalance due toincreased sympathetic activity when the measured heart rate is above ahigher limit value.
 18. The method of claim 17 further comprisingmodifying the higher limit value in accordance with a measured exertionlevel in order to take into account the effects of metabolic demand onautonomic activity.
 19. The method of claim 11 wherein theparasympathetic stimulation is delivered using an endovascularelectrode.
 20. The method of claim 11 further comprising deliveringparasympathetic stimulation at timed intervals when autonomic imbalanceis predicted to be present based upon known circadian rhythms.